Background: Immunotherapy has emerged as an improved systemic treatment for select patients with advanced unresectable HCC. Objective response is reported in 30% of patients, yet complete response (pCR) allowing for curative-intent resection is rare. Locoregional therapies (LRTs) seem to show synergistic effects with immunotherapy, though this effect has not been scientifically reported. We report a cohort of patients showing pCR to immunotherapy + LRT as a proof of concept for the proposed treatment approach for locally unresectable HCC. Methods: Patients with unresectable HCC treated with immunotherapy as an intended destination therapy from 2016 to 2023 were included. The electronic health record was queried for oncologic information, locoregional therapies, surgical interventions, and long-term outcomes. Circulating tumor DNA (ctDNA) testing was obtained using Guardant360, and tumor mutational burden (TMB) was defined as the number of somatic mutations per megabase. Results: Ninety-six patients with advanced HCC received immunotherapy + LRT as a destination therapy. In total, 11 of 96 patients showed a complete response according to mRECIST criteria. Four of these (36.4%) ultimately underwent curative-intent resection. The median follow-up was 24.9 (IQR 15.6–38.3) months. Overall survival rates in those with complete response at 1, 3, and 5 years were 100%, 91%, and 81.8%, respectively, which were significantly improved compared to those of the cohort not achieving pCR (p< 0.001). All four patients undergoing immunotherapy + LRT followed by curative-intent hepatectomy have no evidence of disease (NED). Of those undergoing surgery, ctDNA was cleared in 75% (n = 3), providing an additional objective measurement of complete response. All four patients were TMB+ before beginning this treatment course, with three being TMB-, indicating stable and complete disease response. Conclusions: Immunotherapy + locoregional therapy can help downstage a significant proportion of patients with initially unresectable HCC, allowing for curative-intent surgery. The survival benefit associated with complete response seems durable up to 3 years after achieving this response. ctDNA measurement was converted from positive to negative in this cohort, providing additional indication of response.
背景：免疫疗法已成为部分晚期不可切除肝细胞癌（HCC）患者的新型全身治疗方案。据报道，30%的患者可获得客观缓解，但实现完全缓解（pCR）并接受根治性切除的病例仍属罕见。局部区域治疗（LRTs）与免疫疗法可能具有协同效应，但该效应尚未得到科学验证。本研究通过报告一组经免疫疗法联合局部区域治疗后达到病理完全缓解的病例，为局部不可切除肝细胞癌的治疗方案提供概念验证。 方法：纳入2016年至2023年间接受免疫疗法作为目标治疗的不可切除肝细胞癌患者。通过电子健康记录系统收集肿瘤学信息、局部区域治疗、手术干预及长期预后数据。循环肿瘤DNA（ctDNA）检测采用Guardant360平台，肿瘤突变负荷（TMB）定义为每兆碱基对体细胞突变数量。 结果：96例晚期肝细胞癌患者接受免疫疗法联合局部区域治疗作为目标治疗方案。根据mRECIST标准，其中11例（11/96）达到完全缓解。该亚组中4例患者（36.4%）最终接受根治性切除术。中位随访时间为24.9个月（四分位距15.6-38.3个月）。完全缓解患者的1年、3年和5年总生存率分别为100%、91%和81.8%，显著优于未达到病理完全缓解的队列（p<0.001）。所有4例接受免疫疗法联合局部区域治疗后行根治性肝切除术的患者均无疾病迹象（NED）。手术患者中75%（n=3）的ctDNA检测转阴，为完全缓解提供了客观佐证。治疗前所有4例患者均为TMB阳性，治疗后3例转为TMB阴性，提示疾病获得稳定且完全的缓解。 结论：免疫疗法联合局部区域治疗可使相当比例初始不可切除的肝细胞癌患者实现降期转化，从而获得根治性手术机会。完全缓解带来的生存获益在达到缓解后可持续至少3年。该队列中ctDNA检测由阳性转为阴性，为治疗反应提供了补充性客观指标。
肿瘤(癌症)患者之家